Topic: amyloid-β (Aβ)

A major component of Alzheimer's disease pathology is the accumulation of amyloid-β (Aβ), a peptide that is known to weaken synaptic transmission. Whereas both AMPA receptor (AMPAR) and NMDA receptor (NMDAR) currents are affected by Aβ oligomers, not all synapses are equally vulnerable to the toxic effects of Aβ. We set out to elucidate the roles of the different AMPAR and NMDAR subunits in synapse susceptibility to Aβ. Whole-cell patch clamp recordings were performed in hippocampal CA1 neurons that overexpress Aβ oligomers. Variance analysis was used to disentangle whether this decreased syna

The amyloid-β precursor protein (APP), physiologically cleaved, allows the secretion of Amyloid-β (Aβ) but also of other peptides, including the peptides secreted from the η-secretase pathway (AETA peptides) that we described previously (Willem et al., Nature 2015, PMID:26322584). We now obtained reliable data showing that AETA controls both ionotropic and non-ionotropic signalling of NMDA receptors (NMDAr) (Dunot et al, in revision). Here we asked whether AETA, due to its new-found role as a modulator of NMDArs, could be implicated in Alzheimer’s disease (AD) aetiology. First, we quantified A